Sustained local anesthetic exposure, time-released from injectable or implantable matrices, can greatly improve pain management, including surgical, obstetrical, and neuropathic pain conditions. The goal of this project is to enhance our understanding and clinical treatment of pain through the further development of bioresorpable matrices which produce reversible local anesthetic block. This project focuses on 3-5 days of controlled bupivacaine release to a perisciatic nerve site to produce a pharmacotherapy that is safer and more efficacious than repeated bolus injections. This study also tests the hypothesis that the sustained release of bupivacaine in combination with other analgesics, leads to prolonged local anesthetic effects with greater efficacy, less side- effects, and lower toxicity than the either drug used alone. The proposed investigation involves the following three Specific Aims: 1) The first aim determines the efficacy of sustained local anesthetic release versus repeated bolus injections at a perisciatic nerve site. We hypothesize that sustained release of local anesthetic produces greater block over a longer duration that can be produced by repeated bolus injections. Primary and secondary algesic responses will be assessed in conjunction with biochemical markers of pain. 2) The second aim determines the toxicity of sustained local anesthetic release versus repeated bolus injections at a perisciatic nerve site. We hypothesize that sustained release of local anesthetic diminishes the cytotoxic effects associated with repeated bolus injections of local anesthetic. Inflammatory cells, biochemical markers, glia cell proliferation, and motor deficits will be assessed. 3) Lastly, the third aim determines whether analgesic co-administration reduces inflammation induced by sustained local anesthetic release or repeated bolus injections. We hypothesize that cytotoxic effects are minimized by the co-administration of analgesics at the perisciatic nerve site, given at a delivery dose far below systemic toxicity. Local anesthetic efficacy as in aim 1, toxicity as in aim 2, and the degree of connective tissue encapsulation of the implant will be assessed.